The objective of this research project is a detailed elucidation of the effect of ethanol intoxication, both acute and chronic, on functional and structural parameters of subcellular organelles. It appears probable that the manifestations of hepatic injury may be evident, not only, on a gross level but also in the metabolism of individual cells. With this in mind, we have continued our studies of hepatic endoplasmic reticulum, mitochondria, Golgi complex and plasma membranes. Together with Dr. Charles S. Lieber, we have produced and characterized the entire spectrum of alcoholic liver injury in baboons. After 9 months to 4 years of chronic alcohol ingestion, fatty liver, alcoholic hepatitis and cirrhosis were produced. Citrate was shown to stimulate the fatty acid shuttle for the transport of reducing equivalents into mitochondria, using the disappearance of ethanol in the presence of ADH as the assay system. This effect is presumably caused by citrate-induced stimulation of fatty acid elongation in the mitochondrial membrane. Acetaldehyde was shown to inhibit the shuttles for the transport of reducing equivalents. Such an inhibition by the primary metabolite of ethanol oxidation may play a role in the metabolism of ethanol in vivo. The rate of phospholipid exchange between cell membranes was altered by various experimental regimens, including chronic ethanol intoxication. This was shown to result, not from a change in the organelles, but from an alteration of the soluble fraction. ADH, catalase and MEOS were all shown to have the same stereospecificity. However, the isotope effect was greater with the latter two systems than with ADH. We intend to study mitochondrial changes in baboons fed ethanol, since this species seems to be more sensitive to the effects of ethanol than rats. The function of isolated cells will be studied, and correlated with changes in isolated organelles.